The cyclic somatotropin-release inhibiting factor (SRIF), known as somatostatin, has been shown [Brazeau et al., Science, 179, 77 (1973)] to have the following structure: ##STR2##
Several methods for synthesizing somatostatin have been reported in the literature including the solid phase method of Rivier, J. Am. Chem. Soc., 96, 2986 (1974), and the solution methods of Sarantakis et al., Biochemical Biophysical Research Communications, 54, 234 (1973), and Immer et al., Helv. Chim. Acta, 57, 730 (1974); and there is much on-going peptide research whose goal is to enhance somatostatin's pharmacological activity by synthetically modifying its structure.
The present invention provides novel cyclic analogs of somatostatin wherein its tryptophyl residue may be either of the L or D stereochemical configuration and wherein its ala.sup.1, gly.sup.2, cys.sup.3 and cys.sup.14 residues have been replaced by an .omega.-amino acid of the general formula H.sub.2 N--(CH.sub.2).sub.3-8 --COOH. Replacement of the L-Trp residue in somatostatin by D-Trp is discussed by J. Rivier et al., Biochem. Biophys. Res. Commun., 65, 746 (1975).